Category Archives: Immunotherapy

CO 054: AFFINITY MATURATION AND FINE FUNCTIONAL MAPPING OF AN ANTIBODY FRAGMENT AGAINST A NOVEL NEUTRALIZING EPITOPE ON HUMAN VASCULAR ENDOTHELIAL GROWTH FACTOR

Immunotherapy, Nanomedicine
J Pharm Pharmacogn Res 2(Suppl. 1): S33, 2014

Special supplement with the abstract book of LATINFARMA 2013

Oral Communication

CO 054: AFFINITY MATURATION AND FINE FUNCTIONAL MAPPING OF AN ANTIBODY FRAGMENT AGAINST A NOVEL NEUTRALIZING EPITOPE ON HUMAN VASCULAR ENDOTHELIAL GROWTH FACTOR

Lamdan Ha, Gavilondo JVa, Muñoz Ya, Pupo Ab, Huerta Va, Musacchio Aa, Pérez La, Ayala Ma, Rojas Gb, Balint RFc, Larrick JWd.

aCenter for Genetic Engineering and Biotechnology, La Habana 10600, Cuba. Email: humberto.lamdan@cigb.edu.cu
bCenter of Molecular Immunology, La Habana 11600, Cuba.
cCytoDesign, Inc., Palo Alto, CA 94306, USA.
dPanorama Research Inc., Sunnyvale, CA 94089, USA.
Abstract

Vascular endothelial growth factor (VEGF) is a major mediator of pathological angiogenesis. VEGF antagonists represent attractive candidates as therapeutic agents in the treatment of tumors and other angiogenesis-dependent diseases. Despite the clinical success of Bevacizumab, a humanized monoclonal antibody that blocks the interaction between VEGF and its receptors, the search for new neutralizing antibodies targeting this molecule has continued until now. We used a human VEGF variant containing three mutations in the region recognized by Bevacizumab to direct antibody selection towards recognition of other epitopes. A total of seven phage-displayed antibody fragments were obtained from a human phage display library. All of them were able to recognize not only the selector mutated antigen, but also native VEGF. One of these phage-displayed antibody fragments, denominated 2H1, was shown to compete with the VEGF receptor 2 for VEGF binding. Soluble 2H1 inhibited VEGF biological activity but exhibited a moderate binding affinity. We performed the affinity maturation of 2H1 antibody fragment. Two phage-displayed libraries were constructed by diversification of the third complementarity-determining regions (CDRs) of the light (VL) and heavy (VH) chain variable domains of 2H1 using parsimonious mutagenesis. A competitive phage-selection strategy in the presence of 2H1 as a competitor was used to eliminate low affinity binders. High affinity variants were retrieved from both libraries. An optimized VL variant was constructed by combining recurrent replacements found among selected variants, resulting in an additional affinity increase. Further affinity improvements were achieved by combining this optimized VL with the best VH variants. The final variant, L3H6, showed an overall affinity improvement of 18-fold over the parental antibody and exhibited an enhanced potency to block the binding of VEGF to its receptor. Functional mapping studies of L3H6 using phage display and extensive mutagenesis of VEGF revealed a novel neutralizing epitope on human VEGF.

CO 038: FREQUENCY OF USE OF THE MONOCLONAL ANTIBODY RITUXIMAB ON THE NATIONAL CANCER INSTITUTE OF MEXICO: ONE YEAR EXPERIENCE

Clinical Pharmacology, Immunotherapy, Pharmacoepidemiology
J Pharm Pharmacogn Res 2(Suppl. 1): S20, 2014

Special supplement with the abstract book of LATINFARMA 2013

Oral Communication

CO 038: FREQUENCY OF USE OF THE MONOCLONAL ANTIBODY RITUXIMAB ON THE NATIONAL CANCER INSTITUTE OF MEXICO: ONE YEAR EXPERIENCE

López-Gamboa M1,2, Aguilar-Ponce JL2, Espinoza-Zamora JR2, DavalosFiesco M2, Mena-Rodríguez FJ2, Castañeda-Hernández G1.

1Departamento de Farmacología, Centro de Estudios Avanzados del Instituto Politécnico Nacional, Av. Instituto Politécnico Nacional 2508, San Pedro Zacatenco, C.P. 07360, México D.F.
2Instituto Nacional de Cancerología; Av. San Fernando No. 22, Sol. Sección XVI, C.P. 14080, México D.F. E-mail: dralopezg@gmail.com
Abstract

Introduction: For the health care professionals and for the maker decisions staff on the hospital is very important have a real panorama about the use of the drugs in order to improve the patient attention. In Mexico for the oncology therapeutic segment, Rituximab the chimeric, anti-CD20 monoclonal antibody is registered for: a) the treatment of Non-Hodgking´s Lymphoma (CD20+); b) also combined with chemotherapy for previously untreated patients with relapsed/refractory of chronic lymphocytic leukemia.

Methods: With the aim of determine the Rituximab frequency usage on the National Cancer Institute of Mexico we made a retrospective analysis of the rituximab dispensation data from march 2012 to march 2013. Our collected data were: the pharmaceutical presentation and vials quantity of Rituximab dispensed per patient; and from the clinical record the data recorded included: clinical indication (diagnostic) result of CD20 test, weigh, height, age, and Rituximab dosage prescribed.

Results: During the twelve-month period, a total of 2663 Rituximab vials where dispensed from the Institute pharmacy, 1353 were 500 mg vials, and 1308 were 100 mg vials, distributed on 304 patients. The list of primary diagnostics included 75 different pathologies. All patients had immunohystochemical test, the 95% of the cases were positive to the CD 20 test, 4.7% of the patients had not report and 0.3% were negative to the CD20 test.

Conclusion: Even when Rituximab was prescribed for a diverse range of clinical conditions, the use of CD20 test was a standard followed on the patients, this practice showed the specific use of Rituximab.

CO 023: TRIMETAZIDINE INHIBITS THE RENAL FIBROSIS INDUCED BY CYCLOSPORIN A

Immunotherapy, Preclinical Research
J Pharm Pharmacogn Res 2(Suppl. 1): S12, 2014

Special supplement with the abstract book of LATINFARMA 2013

Oral Communication

CO 023: TRIMETAZIDINE INHIBITS THE RENAL FIBROSIS INDUCED BY CYCLOSPORIN A

De la Cruz Rodríguez L, Rey M, Honoré S, Oldano A, Araujo C.

Facultad de Bioquímica Química y Farmacia. Universidad Nacional de Tucumán, Balcarce 747. (4000) San Miguel de Tucumán, Argentina. E-mail: cdantur@fbqf.unt.edu.ar
Abstract

Introduction: Cyclosporin A (CyA) is an immunosuppressor used in transplanted patients. Adverse effects like as nephrotoxicity and hepatotoxicity, have been described. Our previous papers demonstrated that Trimetazidine (TMZ) is able to reverse the CyAinduced nephrotoxicity.

Objectives: contribute to the knowledge of the mechanisms of action of TMZ in renal fibrosis induced by CyA.

Material and methods: The experimental design was carried out for 120 days. Included four groups (n = 8) of male Wistar rats treated with: A control. B treated with CyA (25 mg/kg/day). C treated with TMZ (20 mg/kg/day). D treated TMZ for 20 days (20 mg/kg/day), them for 120 days with TMZ (20 mg/kg/day) and CyA (25 mg/kg/day). Urea and serum creatinine as well as the excretion of urinary gamma glutamyl transpeptidase were determined. Structural studies were performed with hematoxylin-eosin and Mallory staining to evidence the renal fibrosis. Fibrosis was quantified using the Image Pro Plus software (NIH). By Transmission electron microscope (TEM) the renal ultrastructure was analyzed. Transforming Growth Factor beta and Collagen I were evidenced by immunohistochemistry.

Results: animals treated with 25 mg CyA/kg/day presented hydropic degeneration with nuclei displaced and in some cases are found in the tubular lumen, observed by optical microscopy. Ultrastructure analyzed by TEM showed edematous mitochondria with loss of its internal structure. Interstitial fibrosis was confirmed by evidenced immunohistochemistry Transforming Growth Factor Beta and Collagen I using specific antibodies. Pre-treatment with TMZ for 20 days and the synergistic treatment TMZ+CyA, showed biochemical parameters within the reference values and preserved cytoarchitecture, with negative immunohistochemistry to the markers studied.

Conclusions: Interstitial fibrosis induced by CyA was dose and time dependent. The production of inflammatory mediators, Transforming Growth Factor Beta and the synthesis of Collagen I, would be inhibited by TMZ.

CO 016: CANCER CLINICAL TRIALS: STATE OF THE ART AND THE CUBAN EXPERIENCE

Cancer, Immunotherapy
J Pharm Pharmacogn Res 2(Suppl. 1): S8, 2014

Special supplement with the abstract book of LATINFARMA 2013

Oral Communication

CO 016: CANCER CLINICAL TRIALS: STATE OF THE ART AND THE CUBAN EXPERIENCE

Crombet-Ramos T.

Center of Molecular Immunology, La Habana, Cuba.
Abstract

The old paradigm for oncology drug development was based on the experience of classical cytotoxic agents. According it, antitumor activity is connected to toxicity and therefore, treatments must be scaled up to maximal tolerated dose; pharmacokinetics is relevant to define the optimal schedule; an active drug should produce rapid tumor shrinkage; the response rate is a predictor of survival and tumor progression indicates treatment failure. However, the unique characteristics of biologics challenge these dogmas and demand novel developmental guidelines. For immunotherapy, the optimal biologic dose can be far below the maximal tolerated dose, mechanisms of action can be indirect and therefore not related to pharmacokinetics, effect in survival can be seen without tumor shrinkage and therapeutic effect could be delayed in time and continue beyond progression. The new emerging paradigm recommends finding the optimal biologic dose in a “proof of principle trial” according to a pre-defined biological endpoint or biomarker; followed by an efficacy assessment in a randomized trial with long term treatment and survival as the main endpoint. CIM has now 10 projects in clinical development, including biosimilars and proprietary drugs. The original product pipeline concentrates around 3 main targets: the Epidermal Growth Factor Receptor (EGFR) system, the gangliosides and the regulatory loops of the immune system. Four of the innovative products have already transited through clinical trials and received registration in several countries: the anti-EGFR humanized monoclonal antibody nimotuzumab, the anti-CD6 antibody (itolizumab), the EGF conjugated therapeutic vaccine CimaVax-EGF and the anti-idiotypic vaccine racotumomab. The clinical experience with these products illustrates the application of the new development paradigm intended to transform cancer into a chronic disease.

CO 011: PRECLINICAL EVIDENCES OF P3 MAB IMMUNORESTORATION CAPACITY ON SUPPRESSED BALB/C MICE

Immunotherapy, Preclinical Research
J Pharm Pharmacogn Res 2(Suppl. 1): S6, 2014

Special supplement with the abstract book of LATINFARMA 2013

Oral Communication

CO 011: PRECLINICAL EVIDENCES OF P3 MAB IMMUNORESTORATION CAPACITY ON SUPPRESSED BALB/C MICE

Martínez D, Rodríguez-Zhurbenko N, Griñan T, Rondón T, Vázquez AM, Hernández AM.

Center of Molecular Immunology, Havana, Cuba.
Abstract

Introduction: A fast reconstitution of T cell dependent immunity is a critical issue for patients treated with lymphodepleting regimens. Prolonged period of T cell dysfunction may have serious consequences for the patients, like higher susceptibility to infections, reduced response to vaccines and easier tumor relapse. P3, a murine IgM mAb, recognize N-glycolilated gangliosides, sulphatides and antigens expressed in several human tumors. This antibody has the ability to trigger an IgG antibody response in the syngeneic Balb/c model, even when it is administered without adjuvant or carrier protein. Although the mechanism by which the P3 activates the immune system is unknown, previous experiments show that it is capable of stimulate T cells populations.

Material and methods: We evaluate the importance of T cell populations in the P3 mAb immunogenicity and the capacity of P3 to recover T cells populations on immunosuppressed Balb/c mice, due to tumor or cyclophosphamide treatment.

Results: We show that the high immunogenicity of P3 mAb depends not only on CD4+ but also on CD8+ T cells, since the depletion of CD8+ or CD4+ T cells led to the loss of P3 mAb immunogenicity in the syngeneic model. Furthermore, the immunization with P3 mAb enhanced the recovery of the CD8+ T cell population in mice treated with an anti-CD8a antibody. Additionally, the immunization with P3 mAb restored the capacity of immunosuppressed mice to reject allogeneic tumors, a mechanism mediated by the action of CD8+ T cells. Finally, in mice with cyclophosphamide induced lymphopenia, the administration of P3 mAb accelerated the recovery of both CD4+ and CD8+ T cells.

Conclusions: These results show new possibilities for B and CD8+ T cells interactions during the immune response elicited by a self-protein. Furthermore they point to P3 mAb as a potential interesting candidate for the treatment of immunosuppressed patients.

CO 010: NEOPLASTIC TRANSFORMATION OF HUMAN MESENCHYMAL STEM CELLS CONCERTS IMMUNE-EVASION AND PRO-INFLAMMATORY PROGRAMS IN THE ABSENCE OF IMMUNE-EDITION MEDIATED PREASSURE

Cancer, Immunotherapy
J Pharm Pharmacogn Res 2(Suppl. 1): S6, 2014

Special supplement with the abstract book of LATINFARMA 2013

Oral Communication

CO 010: NEOPLASTIC TRANSFORMATION OF HUMAN MESENCHYMAL STEM CELLS CONCERTS IMMUNE-EVASION AND PRO-INFLAMMATORY PROGRAMS IN THE ABSENCE OF IMMUNE-EDITION MEDIATED PREASSURE

Miranda-Rodríguez A1, Sánchez-Castellanos N1, Funes-Quesada JM2, Pérez-Rodríguez R1, de León-Delgado J1.

1Centro de Inmunología Molecular, La Habana, Cuba. E-mail: alexm@cim.sld.cu
2UCL-Cancer Institute, London, United Kingdom.
Abstract

Introduction: The presence of altered molecular pathways associated with oncogenes and tumor suppressor genes as cancer hallmark not only support the self-sufficiency on tumor cells proliferation but also determine the interaction of neoplastic cells with the host, allowing cells to escape from homeostatic control mechanisms.

The aim of this research is to assess the direct impact of cancer progression driven by genetic alterations over immune-surveillance evasion and tumor related inflammation, in a context independent on immune-edition mediated pressure. We took advantage of a model based on in vitro step-wise neoplastic transformation induced on human mesenchymal stem cells (hMSC). The genetic lesions introduced to transform hMSC included hTERT, c-Myc and H-Ras activity while p53 and pRb expression were reduced.

Methods: MSC immunogenicity was evaluated by HLA-ABC gene and protein expression. In vitro co-culture experiments were performed to determine hMSC inhibitory capacity on T cells proliferation. Immunesuppressive mediators, pro-inflammatory molecules and IFNγ signaling were assessed on hMSCby qPCR, western blot, flow cytometry, ELISA, gene micro-array and immune-fluorescence assays. Neoplastic hMSC with reduced expression of IL-beta were obtained by lentiviral infection encoding shRNA targeting IL-beta mRNA. Anchorage independent growth in soft agar was assayed as surrogate of cells tumorigenicity. In vivo tumorigenicity was evaluated by xenogenic transplantation in athymic nude mice.

Results: In vitro step-wise neoplastic transformation reduces hMSC immunogenicity and progressively increases the inhibitory capacity of hMSC on T cell proliferation, whereas a modification in the immunesuppressive mechanism is detected. Transformation leads to the generation of a pro-inflammatory phenotype characterized by increased expression of IL-beta, a mediator that concert tumorigenic and immune-suppressive potential of fully transformed cells.

Conclusions: Overall results suggest that neoplastic transformation can stimulate oncogenic inflammation and immune-surveillance evasion as an intrinsic feature of cancer cells, even in the absence of the immune-edition pressure exerted at tumor microenvironment.

CO 008: IMMUNOTRANS-ARTERIAL CHEMOEMBOLIZATION (ITACE) IN HEPATOCELLULAR CARCINOMA PATIENTS TREATED WITH ANTI-EGFR MAB NIMOTUZUMAB PLUS ADRIAMYCIN. PHASE I CLINICAL TRIAL, FINAL RESULTS

Cancer, Immunotherapy
J Pharm Pharmacogn Res 2(Suppl. 1): S5, 2014

Special supplement with the abstract book of LATINFARMA 2013

Oral Communication

CO 008: IMMUNOTRANS-ARTERIAL CHEMOEMBOLIZATION (ITACE) IN HEPATOCELLULAR CARCINOMA PATIENTS TREATED WITH ANTI-EGFR MAB NIMOTUZUMAB PLUS ADRIAMYCIN. PHASE I CLINICAL TRIAL, FINAL RESULTS

Ramos-Suzarte M1, Hernández JC2, Roque A2, Ugarte JC2, Jordán J2, Samada M2, Lorenzo P1, Fernández A1, Catalá M2, Fermín E2, Frías A1, Izquierdo M1, Cedeño M1, Rengifo E1, Frómeta M1, Crombet T.1

1Center of Molecular Immunology, Havana, Cuba. E-mail: mayra@cim.sld.cu
2Center for Medical and Surgical Research, Havana, Cuba.
Abstract

Introduction: Hepatocellular carcinoma (HCC) is a common complication of chronic liver disease. EGFR is well validated as a primary contributor of different tumor of epithelial origin included liver cancer in initiation and progression. Nimotuzumab is a humanized monoclonal antibody (mAbs) that recognizes the EGFR extracellular domain. While it has similar preclinical and clinical activity when compared to other anti-EGFR mAbs, it does not induce skin toxicity or hypomagnesaemia.

Methods: Phase I prospective clinical trial (RPCEC00000022) to evaluate safety and optimal biological doses of immunotrans-arterial chemoembolization (ITACE) with nimotuzumab in patients with unresectable HCC. In this trial were enrolled 3 patients in 4 different level doses of Mab: 50 mg, 100 mg, 200 mg and 400 mg maintaining the same concentration of cytostatic drug per level, just one administration per patients. The principal endpoint was evaluate safety and Optimal or Maxima Biological Doses in the treatment of HCC by Trans arterial chemoembolization (ITACE) by injecting nimotuzumab an doxorubicin mixed with a radiopaque contrast (e.g. Lipiodol) and an embolic agent Gel foam into hepatic artery.

Results: The maximum tolerable dose was 200 mg of nimotuzumab, was impossible complete the administration in 400 mg because the administration rout was intra-arterial and the limiting factor was the final volume. Was confirmed a gain for these patients, since the life expectancy of them were about 6 months however median survival of 13.01 months was found to be above expected. Nimotuzumab was safe in terms of intra-arterial administration and the combination with doxorubicin. Not anti-idiotipic response was detected in any treated patients. Was the first time that nimotuzumab was administered by intra-arterial rout but is a perfect way to be used in this tumor.

Conclusions: The maxima tolerated dose was 200 mg of nimotuzumab for ITACE. The administration of nimotuzumab was safety, increasing patient survival, which provides a longer period for the possibility for patients to receive a liver transplant. The combinations with chemotherapy not increase the toxicity of therapy.

CO 004: In Silico DESIGN AND FUNCTIONAL CHARACTERIZATION OF A TGFβ1 MUTEIN, ANTAGONISTIC OF TGFβ SIGNALING, WITH ANTITUMOR AND IMMUNOMODULATORS PROPERTIES

Cancer, Immunotherapy, Preclinical Research
J Pharm Pharmacogn Res 2(Suppl. 1): S3, 2014

Special supplement with the abstract book of LATINFARMA 2013

Oral Communication

CO 004: In Silico DESIGN AND FUNCTIONAL CHARACTERIZATION OF A TGFβ1 MUTEIN, ANTAGONISTIC OF TGFβ SIGNALING, WITH ANTITUMOR AND IMMUNOMODULATORS PROPERTIES

Corría Osorio J, Pérez Rodríguez S, Carmenate Portilla T, León Monzón K.

System Biology Department. Center of Molecular Immunology, Havana, Cuba. Email: jesus@cim.sld.cu
Abstract

Introduction: Transforming growth factor β (TGFβ) is pleiotropic cytokine that affects tumor growth, metastasis, stroma, and immune response. There are three isoforms: TGFβ1, TGFβ2, and TGFβ3. They interact on the cell surface with the TβRII receptor, TβRIII receptor and several of the type I receptors that have been described (ALK5, ALK1, ALK2, ALK3); ALK5 is the clasic type I receptor of these ligands. It has been proposed that the ligands bind first to TβRIII and then this receptor transfers them to TβRII receptor. TGFβ1 and TGFβ3 can bind to TβRII receptor with high affinity (5-30 pM) whereas TGFβ2 has 1000 fold less affinity. ALK5 is recruited and activated in a highly cooperative manner by the TβRII/TGFβ complex, forming the heterotrimeric signaling complex. The ALK5 signaling plays a pivotal role in regulating the pathogenesis of a wide variety of disorders including cancer. Blockade of TGFβ signaling has been reported to be efficacious in the suppression of tumor growth and metastasis in animal models and clinical trials. In the present work we described for first time, a TGFβ1 mutein that behave as an antagonistic of the TGFβ signaling and has antitumor and immunemodulators effects in vitro.

Material and methods: This mutein was designed using several bioinformatics tool such as 3DCoffee and clustalX for the evolutionary analysis, the web server Protein Interaction Calculator was used to determine principals interactions in the interface, and Rosetta to determine hot spot residues and destabilizing mutations This mutein was fused to a human IgG1 Fc region with a set of mutations in the the Cγ2 domain that abrogates the binding with Fc gamma receptors except the neonatal. The fusion to Fc region was useful for expressing, for first time, the TGFβ domain without its latency associated propeptide (LAP) that is very important because the mutein can be obtained in its active form to interact with TβRII receptor. TGFβ1 mutein.Fc was obtained using a lentiviral transduction protocol in CHO-K1 cells. Evaluation of the antagonistic effects was done in IL-2– dependent CTLL-2 cell proliferation assay, TGFβ1-induced Treg differentiations assays and in vitro tumor cell migration assay.

Results: TGFβ1Mut_Fc had less biological activity than recombinant TGFβ1 and blocked TGFβ1-stimulated inhibition of IL-2–dependent CTLL-2 cell proliferation. Also, TGFβ1Mut_Fc inhibited the generation of foxp3 positive CD4+ T cells induced by wtTGFβ1. Finally, TGFβ1Mut_Fc inhibited tumor cell migration in vitro.

Conclusions: The TGFβ1 mutein.Fc behaves as an antagonistic of TGFβ signaling and that suggest that the destabilizing mutations predicted by using bioinformatics tool affect interaction between TGFβ1 and ALK5. These data provide a foundation to support using TGFβ1 mutein_Fc as a therapeutic agent for TGFβ-dependent cancer with metastatic and immuneregulatory capacity.

CO 001: TOWARDS CLINICAL TRANSLATION OF T-CELL RECEPTOR GENE EDITING TO MEDIATE ADOPTIVE ANTITUMOR IMMUNOTHERAPY

Cancer, Immunotherapy
J Pharm Pharmacogn Res 2(Suppl. 1): S2, 2014

Special supplement with the abstract book of LATINFARMA 2013

Oral Communication

CO 001: TOWARDS CLINICAL TRANSLATION OF T-CELL RECEPTOR GENE EDITING TO MEDIATE ADOPTIVE ANTITUMOR IMMUNOTHERAPY

Ciceri F, Mastaglio S, Bonini C.

Experimental Hematology Unit, San Raffaele Scientific Institute, Milan, Italy.
Abstract

Introduction: The genetic addition of a tumor specific receptor into T cells yielded already substantial clinical results in patients affected by hematological malignancies.

Methods: To completely substitute T cell specificity, we recently developed the TCR gene editing approach, based on the combination of: i. Somatic knockout of the endogenous TCR genes (achieved by transient exposure to β- and α-chain specific Zinc Finger NucleasesZFN), and ii. Introduction of a tumor-specific TCR by lentiviral vectors (LV). By avoiding competition for surface expression between exogenous and endogenous TCR β- and α-chains, and by abrogating the risk of inappropriate TCR pairing, the TCR editing approach permanently overcomes the major limitations of TCR gene transfer (Provasi, Genovese et al., Nat. Med. 2012).

Results: To promote an effective and persistent therapeutic effect, and to facilitate its clinical application, we established a scalable protocol of TCR single editing, applicable within a single round of T cell stimulation. This approach completely and permanently abrogates expression of the endogenous TCR repertoire of donor T cells, which is responsible of GvHD. In addition, we validated the TCR editing approach on NY-ESO-1, expressed by solid tumors and hematological malignancies. We observed similar high levels of TCR expression, measured by NY-ESO-1 specific dextramer binding, in single edited and transferred T cells (RFI 73 vs. 66). Single edited cells efficiently recognized and killed NY-ESO-1+ myeloma cell lines, without aberrant response to NY-ESO-1- targets, and displayed improved tumor specificity than unedited TCR-transferred cells in co-culture assays (99% of elimination of target cells in both single edited and transferred cells; 0% vs. 45.9% of elimination of unspecific targets, respectively).

Conclusions: These results suggest that the TCR gene editing approach can mediate Graft versus Tumor and overcome the risk of GvHD in patients with hematological malignancies undergoing allo-HSCT.

C 033: IMMUNOTHERAPY FOR NON HODGKIN’S LYMPHOMAS. ADVANCES IN THE USE OF MONOCLONAL ANTIBODIES

Cancer, Immunotherapy
J Pharm Pharmacogn Res 2(Suppl. 1): S99, 2014

Special supplement with the abstract book of LATINFARMA 2013

Conference

C 033: IMMUNOTHERAPY FOR NON HODGKIN’S LYMPHOMAS. ADVANCES IN THE USE OF MONOCLONAL ANTIBODIES

Gracia Medina E.

Medical Oncology Department. National Institute of Oncology and Radiobiology, La Habana, Cuba.
Abstract

Immunotherapy has been used systematically for the treatment of non Hodgkin’s Lymphomas (NHL). Modifier of immune response, monoclonal antibodies (MAb) and therapeutics cancer vaccines have shown different grade of outcomes in the management of this heterogeneous disease.

Over the last ten years, the introduction of monoclonal antibodies (MAbs) and specifically the anti-CD20 monoclonal antibody Rituximab has radically changed treatment of B-cell NHL. The use of Rituximab in the treatment of such lymphomas has increased significantly the response rates, the progression free survival and overall survival in both indolent and aggressive B-cell NHL. Based in the results achieved with this drug new strategies of treatment have been developed using MAbs against different epitopes of the CD20 molecule and against other molecules expressed in the surface of lymphoma cell such as CD19, CD22, CD37 and CD30. Moreover, the new drugs such as conjugated antibodies, which are design to carry cytotoxic inside to the target cell; bivalents MAb, and MAb against molecules that regulate the immune response are showing encourages results and they are rapidly moving into efficacy studies. In this review we present the advances in the use of MAb for the treatment of NHL.